TY - JOUR
T1 - T-cell infiltration and clonality correlate with programmed cell death protein 1 and programmed death-ligand 1 expression in patients with soft tissue sarcomas
AU - Pollack, Seth M.
AU - He, Qianchuan
AU - Yearley, Jennifer H.
AU - Emerson, Ryan
AU - Vignali, Marissa
AU - Zhang, Yuzheng
AU - Redman, Mary W.
AU - Baker, Kelsey K.
AU - Cooper, Sara
AU - Donahue, Bailey
AU - Loggers, Elizabeth T.
AU - Cranmer, Lee D.
AU - Spraker, Matthew B.
AU - Seo, Y. David
AU - Pillarisetty, Venu G.
AU - Ricciotti, Robert W.
AU - Hoch, Benjamin L.
AU - McClanahan, Terrill K.
AU - Murphy, Erin
AU - Blumenschein, Wendy M.
AU - Townson, Steven M.
AU - Benzeno, Sharon
AU - Riddell, Stanley R.
AU - Jones, Robin L.
N1 - Publisher Copyright:
© 2017 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.
PY - 2017/9/1
Y1 - 2017/9/1
N2 - BACKGROUND: Patients with metastatic sarcomas have poor outcomes and although the disease may be amenable to immunotherapies, information regarding the immunologic profiles of soft tissue sarcoma (STS) subtypes is limited. METHODS: The authors identified patients with the common STS subtypes: leiomyosarcoma, undifferentiated pleomorphic sarcoma (UPS), synovial sarcoma (SS), well-differentiated/dedifferentiated liposarcoma, and myxoid/round cell liposarcoma. Gene expression, immunohistochemistry for programmed cell death protein (PD-1) and programmed death-ligand 1 (PD-L1), and T-cell receptor Vβ gene sequencing were performed on formalin-fixed, paraffin-embedded tumors from 81 patients. Differences in liposarcoma subsets also were evaluated. RESULTS: UPS and leiomyosarcoma had high expression levels of genes related to antigen presentation and T-cell infiltration. UPS were found to have higher levels of PD-L1 (P≤.001) and PD-1 (P≤.05) on immunohistochemistry and had the highest T-cell infiltration based on T-cell receptor sequencing, significantly more than SS, which had the lowest (P≤.05). T-cell infiltrates in UPS also were more oligoclonal compared with SS and liposarcoma (P≤.05). A model adjusted for STS histologic subtype found that for all sarcomas, T-cell infiltration and clonality were highly correlated with PD-1 and PD-L1 expression levels (P≤.01). CONCLUSIONS: In the current study, the authors provide the most detailed overview of the immune microenvironment in sarcoma subtypes to date. UPS, which is a more highly mutated STS subtype, provokes a substantial immune response, suggesting that it may be well suited to treatment with immune checkpoint inhibitors. The SS and liposarcoma subsets are less mutated but do express immunogenic self-antigens, and therefore strategies to improve antigen presentation and T-cell infiltration may allow for successful immunotherapy in patients with these diagnoses. Cancer 2017;123:3291-304.
AB - BACKGROUND: Patients with metastatic sarcomas have poor outcomes and although the disease may be amenable to immunotherapies, information regarding the immunologic profiles of soft tissue sarcoma (STS) subtypes is limited. METHODS: The authors identified patients with the common STS subtypes: leiomyosarcoma, undifferentiated pleomorphic sarcoma (UPS), synovial sarcoma (SS), well-differentiated/dedifferentiated liposarcoma, and myxoid/round cell liposarcoma. Gene expression, immunohistochemistry for programmed cell death protein (PD-1) and programmed death-ligand 1 (PD-L1), and T-cell receptor Vβ gene sequencing were performed on formalin-fixed, paraffin-embedded tumors from 81 patients. Differences in liposarcoma subsets also were evaluated. RESULTS: UPS and leiomyosarcoma had high expression levels of genes related to antigen presentation and T-cell infiltration. UPS were found to have higher levels of PD-L1 (P≤.001) and PD-1 (P≤.05) on immunohistochemistry and had the highest T-cell infiltration based on T-cell receptor sequencing, significantly more than SS, which had the lowest (P≤.05). T-cell infiltrates in UPS also were more oligoclonal compared with SS and liposarcoma (P≤.05). A model adjusted for STS histologic subtype found that for all sarcomas, T-cell infiltration and clonality were highly correlated with PD-1 and PD-L1 expression levels (P≤.01). CONCLUSIONS: In the current study, the authors provide the most detailed overview of the immune microenvironment in sarcoma subtypes to date. UPS, which is a more highly mutated STS subtype, provokes a substantial immune response, suggesting that it may be well suited to treatment with immune checkpoint inhibitors. The SS and liposarcoma subsets are less mutated but do express immunogenic self-antigens, and therefore strategies to improve antigen presentation and T-cell infiltration may allow for successful immunotherapy in patients with these diagnoses. Cancer 2017;123:3291-304.
KW - T-cell receptors
KW - gene expression
KW - immunotherapy
KW - leiomyosarcoma
KW - liposarcoma
KW - pleomorphic
KW - programmed cell death protein (PD-1)
KW - programmed death-ligand 1 (PD-L1)
KW - sarcoma
UR - http://www.scopus.com/inward/record.url?scp=85018743172&partnerID=8YFLogxK
U2 - 10.1002/cncr.30726
DO - 10.1002/cncr.30726
M3 - Article
C2 - 28463396
AN - SCOPUS:85018743172
SN - 0008-543X
VL - 123
SP - 3291
EP - 3304
JO - Cancer
JF - Cancer
IS - 17
ER -